Skip to main content
Top
Published in: European Journal of Nutrition 1/2013

01-02-2013 | Original Contribution

Endothelium/nitric oxide mechanism mediates vasorelaxation and counteracts vasoconstriction induced by low concentration of flavanols

Authors: Annalisa Aggio, Davide Grassi, Eugenia Onori, Antonio D’Alessandro, Francesco Masedu, Marco Valenti, Claudio Ferri

Published in: European Journal of Nutrition | Issue 1/2013

Login to get access

Abstract

Purpose

At relatively low concentrations, flavanols induce inconsistent effects on isolated arterial tone, sometimes explained as being due to a structure–activity relationship. The aim of our study was to investigate the effects of two flavanols at different doses on arterial functional state.

Methods

The effects of two catechins, (−)-epigallocatechin-3-gallate (EGCG) and (−)-epicatechin (EP), on rat-isolated aorta tone were investigated on resting tension and on precontracted preparations, both in the presence and in the absence of endothelium.

Results

At resting tension, endothelium-intact preparations, EGCG and EP (0.01–10 μM), induced a slight concentration-dependent, non-significant contraction. On endothelium-denuded preparations, both EGCG and EP induced a concentration-dependent contraction (significance at 0.1 and 1 μM concentrations of the two compounds, respectively). In phenylephrine (PE) (1 μM) precontracted, endothelium-intact preparations, EGCG and EP (0.01–10 μM), induced a concentration-dependent vasorelaxation, reaching significance at 1 μM concentration of both agonists. On endothelium-denuded preparations, EGCG and EP did not significantly affect PE (0.3 μM)-induced tone. In endothelium-intact precontracted preparations, Nω nitro-l-arginine (L-NNA), a nitric oxide synthase (NOS) activity inhibitor, abolished the vasorelaxant effect of EGCG and EP (0.01–10 μM). At high concentrations, EGCG and EP (100 μM) elicited a marked relaxation. This was significantly larger in the presence than in the absence of endothelium or in the presence of L-NNA.

Conclusions

Our findings highlight the important role played by an endothelium/NO-mechanism in the regulation of basal tone and in both mediating vasorelaxation and counteracting vasoconstriction induced by low concentrations of flavanols in rat thoracic aorta.
Literature
1.
go back to reference Vita JA (2003) Tea consumption and cardiovascular disease: effects on endothelial function. J Nutr 133:3293S–3297S Vita JA (2003) Tea consumption and cardiovascular disease: effects on endothelial function. J Nutr 133:3293S–3297S
2.
go back to reference Kuriyama S, Hozawa A, Ohmori K, Shimazu T, Matsui T, Ebihara S, Awata S, Nagatomi R, Arai H, Tsuji I (2006) Green tea consumption and mortality due to cardiovascular disease, cancer, and all causes in Japan. Am J Clin Nutr 83:355–361 Kuriyama S, Hozawa A, Ohmori K, Shimazu T, Matsui T, Ebihara S, Awata S, Nagatomi R, Arai H, Tsuji I (2006) Green tea consumption and mortality due to cardiovascular disease, cancer, and all causes in Japan. Am J Clin Nutr 83:355–361
3.
go back to reference Widlansky ME, Hamburg NM, Anter E, Holbrook M, Kahn DF, Elliott JG, Keaney JF Jr, Vita JA (2007) Acute EGCG supplementation reverses endothelial dysfunction in patients with coronary artery disease. J Am Coll Nutr 2:95–102 Widlansky ME, Hamburg NM, Anter E, Holbrook M, Kahn DF, Elliott JG, Keaney JF Jr, Vita JA (2007) Acute EGCG supplementation reverses endothelial dysfunction in patients with coronary artery disease. J Am Coll Nutr 2:95–102
4.
go back to reference Duffy SJ, Keaney JF Jr, Holbrook M, Gokce N, Swerdloff PL, Frei B, Vita JA (2001) Short- and long-term black tea consumption reverses endothelial dysfunction in patients with coronary artery disease. Circulation 104:151–156CrossRef Duffy SJ, Keaney JF Jr, Holbrook M, Gokce N, Swerdloff PL, Frei B, Vita JA (2001) Short- and long-term black tea consumption reverses endothelial dysfunction in patients with coronary artery disease. Circulation 104:151–156CrossRef
5.
go back to reference Schroeter H, Heiss C, Balzer J et al (2006) (−)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans. PNAS 103:1024–1029CrossRef Schroeter H, Heiss C, Balzer J et al (2006) (−)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans. PNAS 103:1024–1029CrossRef
6.
go back to reference Engler MB, Engler MM, Chen CY, Malloy MJ, Browne A, Chiu EY, Kwak HK, Milbury P, Paul SM, Blumberg J, Mietus-Snyder ML (2004) Flavanoid-rich dark chocolate improves endothelial function and increases plasma epicatechin concentrations in healthy adults. J Am Coll Nutr 23:197–204 Engler MB, Engler MM, Chen CY, Malloy MJ, Browne A, Chiu EY, Kwak HK, Milbury P, Paul SM, Blumberg J, Mietus-Snyder ML (2004) Flavanoid-rich dark chocolate improves endothelial function and increases plasma epicatechin concentrations in healthy adults. J Am Coll Nutr 23:197–204
7.
go back to reference Matsui T, Korematsu S, Byun EB, Nishizuka T, Ohshima S, Kanda T (2009) Apple procyanidins induced vascular relaxation in isolated rat aorta through NO/cGMP pathway in combination with hyperpolarization by multiple K+ channel activations. Biosci Biochem Biotechnol 73:2246–2251CrossRef Matsui T, Korematsu S, Byun EB, Nishizuka T, Ohshima S, Kanda T (2009) Apple procyanidins induced vascular relaxation in isolated rat aorta through NO/cGMP pathway in combination with hyperpolarization by multiple K+ channel activations. Biosci Biochem Biotechnol 73:2246–2251CrossRef
8.
go back to reference Grassi D, Lippi C, Necozione S, Desideri G, Ferri C (2005) Short-term administration of dark chocolate is followed by a significant increase in insulin sensitivity and a decrease in blood pressure in healthy persons. Am J Clin Nutr 81:611–614 Grassi D, Lippi C, Necozione S, Desideri G, Ferri C (2005) Short-term administration of dark chocolate is followed by a significant increase in insulin sensitivity and a decrease in blood pressure in healthy persons. Am J Clin Nutr 81:611–614
9.
go back to reference Grassi D, Desideri G, Necozione S, Lippi C, Casale R, Properzi G, Blumberg JB, Ferri C (2008) Blood pressure is reduced and insulin sensitivity increased in glucose-intolerant, hypertensive subjects after 15 days of consuming high-polyphenol dark chocolate. J Nutr 138:1671–1676 Grassi D, Desideri G, Necozione S, Lippi C, Casale R, Properzi G, Blumberg JB, Ferri C (2008) Blood pressure is reduced and insulin sensitivity increased in glucose-intolerant, hypertensive subjects after 15 days of consuming high-polyphenol dark chocolate. J Nutr 138:1671–1676
10.
go back to reference Corretti MC, Anderson TJ, Benjamin EJ et al (2002) International Brachial Artery Reactivity Task Force. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol 16:257–265CrossRef Corretti MC, Anderson TJ, Benjamin EJ et al (2002) International Brachial Artery Reactivity Task Force. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol 16:257–265CrossRef
11.
go back to reference Rice-Evans CA, Miller NJ, Paganga G (1996) Structure-antioxidant activity relationships of flavanoids and phenolic acids. Free Radic Biol Med 20:933–956CrossRef Rice-Evans CA, Miller NJ, Paganga G (1996) Structure-antioxidant activity relationships of flavanoids and phenolic acids. Free Radic Biol Med 20:933–956CrossRef
12.
go back to reference Richelle M, Tavazzi I, Enslen M, Offord EA (1999) Plasma kinetics in man of epicatechin from black chocolate. Eur J Clin Nutr 53:22–26CrossRef Richelle M, Tavazzi I, Enslen M, Offord EA (1999) Plasma kinetics in man of epicatechin from black chocolate. Eur J Clin Nutr 53:22–26CrossRef
13.
go back to reference Auger C, Kim JH, Chabert P, Chaabi M, Anselm E, Lanciaux X, Lobstein A, Schini-Kerth VB (2010) The EGCg-induced redox-sensitive activation of endothelial nitric oxide synthase and relaxation are critically dependent on hydroxyl moieties. Biochem Biophys Res Commun 393:162–167CrossRef Auger C, Kim JH, Chabert P, Chaabi M, Anselm E, Lanciaux X, Lobstein A, Schini-Kerth VB (2010) The EGCg-induced redox-sensitive activation of endothelial nitric oxide synthase and relaxation are critically dependent on hydroxyl moieties. Biochem Biophys Res Commun 393:162–167CrossRef
14.
go back to reference Ramirez-Sanchez I, Maya L, Ceballos G, Villarreal F (2010) (−)-Epicatechin activation of endothelial cell endothelial nitric oxide synthase, nitric oxide, and related signaling pathways. Hypertension 55:1398–1405CrossRef Ramirez-Sanchez I, Maya L, Ceballos G, Villarreal F (2010) (−)-Epicatechin activation of endothelial cell endothelial nitric oxide synthase, nitric oxide, and related signaling pathways. Hypertension 55:1398–1405CrossRef
15.
go back to reference Moore RJ, Jackson KG, Minihane AM (2009) Green tea (Camellia sinensis) catechins and vascular function. Br J Nutr 102:1790–1802CrossRef Moore RJ, Jackson KG, Minihane AM (2009) Green tea (Camellia sinensis) catechins and vascular function. Br J Nutr 102:1790–1802CrossRef
16.
go back to reference Duarte J, Vizcaino P, Zarzuelo A, Jimenez J, Tamargo J (1993) Vasodilatator effects of quercetin in isolated rat vascular smooth muscle. Eur J Pharmacol 239:1–7CrossRef Duarte J, Vizcaino P, Zarzuelo A, Jimenez J, Tamargo J (1993) Vasodilatator effects of quercetin in isolated rat vascular smooth muscle. Eur J Pharmacol 239:1–7CrossRef
17.
go back to reference Herrera MD, Zarzuelo A, Jimenez J, Marhuenda E, Duarte J (1996) Effects of flavonoids on rat aortic smooth muscle contractility: structure-activity relationships. Gen Pharmac 27:273–277CrossRef Herrera MD, Zarzuelo A, Jimenez J, Marhuenda E, Duarte J (1996) Effects of flavonoids on rat aortic smooth muscle contractility: structure-activity relationships. Gen Pharmac 27:273–277CrossRef
18.
go back to reference Chan ECH, Pannangpetch P, Woodman OL (2000) Relaxation to flavones and flavonols in rat isolated thoracic aorta: mechanism of action and structure-activity relationships. J Cardiovasc Pharmacol 35:326–333CrossRef Chan ECH, Pannangpetch P, Woodman OL (2000) Relaxation to flavones and flavonols in rat isolated thoracic aorta: mechanism of action and structure-activity relationships. J Cardiovasc Pharmacol 35:326–333CrossRef
19.
go back to reference Woodman OL, Meeker WF, Boujaoude M (2005) Vasorelaxant and antioxidant activity of flavanols and flavones: structure-activity relationships. J Cardiovasc Pharmacol 46:302–309CrossRef Woodman OL, Meeker WF, Boujaoude M (2005) Vasorelaxant and antioxidant activity of flavanols and flavones: structure-activity relationships. J Cardiovasc Pharmacol 46:302–309CrossRef
20.
go back to reference Sanae F, Miyaichi Y, Kizu H, Hayashi H (2002) Effect of catechins on vascular tone in rat aortic thoracic aorta with endothelium. Life Sci 71:2553–2562CrossRef Sanae F, Miyaichi Y, Kizu H, Hayashi H (2002) Effect of catechins on vascular tone in rat aortic thoracic aorta with endothelium. Life Sci 71:2553–2562CrossRef
21.
go back to reference Lorenz M, Wessler S, Follmann E et al (2004) A constituent of green tea, epigallocatechin-3-gallate, activates endothelial nitric oxide synthase by a phosphatidylinositol-3-OH-kinase-, cAMP-dependent protein kinase-, and Akt-dependent pathway and leads to endothelial-dependent vasorelaxation. J Biol Chem 279:6190–6195CrossRef Lorenz M, Wessler S, Follmann E et al (2004) A constituent of green tea, epigallocatechin-3-gallate, activates endothelial nitric oxide synthase by a phosphatidylinositol-3-OH-kinase-, cAMP-dependent protein kinase-, and Akt-dependent pathway and leads to endothelial-dependent vasorelaxation. J Biol Chem 279:6190–6195CrossRef
22.
go back to reference Lorenz M, Urban J, Engelhardt U, Baumann G, Stangl K, Stangl V (2009) Green and black tea are equally potent stimuli of NO production and vasodilation: new insights into tea ingredients involved. Basic Res Cardiol 104:100–110CrossRef Lorenz M, Urban J, Engelhardt U, Baumann G, Stangl K, Stangl V (2009) Green and black tea are equally potent stimuli of NO production and vasodilation: new insights into tea ingredients involved. Basic Res Cardiol 104:100–110CrossRef
23.
go back to reference Lim DY, Lee ES, Park HG, Kim BC, Hong SP, Lee EB (2003) Comparison of green tea extract and epigallocatechin gallate on blood pressure and contractile responses of vascular smooth muscle of rats. Arch Pharm Res 26:214–223CrossRef Lim DY, Lee ES, Park HG, Kim BC, Hong SP, Lee EB (2003) Comparison of green tea extract and epigallocatechin gallate on blood pressure and contractile responses of vascular smooth muscle of rats. Arch Pharm Res 26:214–223CrossRef
24.
go back to reference Angus JA, Wrigth CE (2000) Techniques to study the pharmacodynamics of isolated large and small blood vessel. J Pharmacol Toxicol Methods 44:395–407CrossRef Angus JA, Wrigth CE (2000) Techniques to study the pharmacodynamics of isolated large and small blood vessel. J Pharmacol Toxicol Methods 44:395–407CrossRef
25.
go back to reference Nishimura K, Ota M, Ito K (1991) Existence of two components in the tonic contraction of rat aorta mediated by α1-adrenoceptor activation. Br J Pharmacol 102:215–221CrossRef Nishimura K, Ota M, Ito K (1991) Existence of two components in the tonic contraction of rat aorta mediated by α1-adrenoceptor activation. Br J Pharmacol 102:215–221CrossRef
26.
go back to reference Ajay M, Gilani AH, Mustafa MR (2003) Effects of flavonoids on vascular smooth muscle of the isolated rat thoracic aorta. Life Sci 74:603–612CrossRef Ajay M, Gilani AH, Mustafa MR (2003) Effects of flavonoids on vascular smooth muscle of the isolated rat thoracic aorta. Life Sci 74:603–612CrossRef
27.
go back to reference Shen JZ, Zheng XF, Wei EQ, Kwan CY (2003) Green tea catechins evoke a phasic contraction in rat aorta via H2O2-mediated multiple-signalling pathways. Clin Exp Pharmacol Physiol 30:88–95CrossRef Shen JZ, Zheng XF, Wei EQ, Kwan CY (2003) Green tea catechins evoke a phasic contraction in rat aorta via H2O2-mediated multiple-signalling pathways. Clin Exp Pharmacol Physiol 30:88–95CrossRef
28.
go back to reference Schrammel A, Behrends S, Schmidt K, Koesling D, Mayer B (1996) Characterization of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one as a heme-site inhibitor of nitric oxide-sensitive guanylyl cyclase. Mol Pharmacol 50:1–6 Schrammel A, Behrends S, Schmidt K, Koesling D, Mayer B (1996) Characterization of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one as a heme-site inhibitor of nitric oxide-sensitive guanylyl cyclase. Mol Pharmacol 50:1–6
29.
go back to reference Alvarez-Castro E, Campos-Tomoil M, Orallo F (2004) (−)-Epigallocatechin-3-gallate induces contraction of the rat aorta by a calcium influx-dependent mechanism. Naunyn-Schmiedeberg’s Arch Pharmacol 369:496–506CrossRef Alvarez-Castro E, Campos-Tomoil M, Orallo F (2004) (−)-Epigallocatechin-3-gallate induces contraction of the rat aorta by a calcium influx-dependent mechanism. Naunyn-Schmiedeberg’s Arch Pharmacol 369:496–506CrossRef
30.
go back to reference Loke WM, Hodgson JM, Proudfoot JM, McKinley AJ, Puddey IB, Croft KD (2008) Pure dietary flavonoids quercetin and (−)-epicatechin augment nitric oxide products and reduce endothelin-1 acutely in healthy men. Am J Clin Nutr 88:1018–1025 Loke WM, Hodgson JM, Proudfoot JM, McKinley AJ, Puddey IB, Croft KD (2008) Pure dietary flavonoids quercetin and (−)-epicatechin augment nitric oxide products and reduce endothelin-1 acutely in healthy men. Am J Clin Nutr 88:1018–1025
31.
go back to reference Huang Y, Chan NW, Lau CW, Yao XQ, Chan FL, Chen ZY (1999) Involvement of endothelium/nitric oxide in vasorelaxation induced by purified green tea (−)epicatechin. Biochim Biophys Acta 1427:322–328CrossRef Huang Y, Chan NW, Lau CW, Yao XQ, Chan FL, Chen ZY (1999) Involvement of endothelium/nitric oxide in vasorelaxation induced by purified green tea (−)epicatechin. Biochim Biophys Acta 1427:322–328CrossRef
32.
go back to reference Kim JA, Formoso G, Li Y, Potenza MA, Marasciulo FL, Montagnani M, Quon MJ (2007) Epigallocatechin gallate, a green tea polyphenol, mediates NO-dependent vasodilation using signaling pathways in vascular endothelium requiring reactive oxygen species and Fyn. J Biol Chem 282:13736–13745CrossRef Kim JA, Formoso G, Li Y, Potenza MA, Marasciulo FL, Montagnani M, Quon MJ (2007) Epigallocatechin gallate, a green tea polyphenol, mediates NO-dependent vasodilation using signaling pathways in vascular endothelium requiring reactive oxygen species and Fyn. J Biol Chem 282:13736–13745CrossRef
33.
go back to reference Alvarez E, Campos-Toimil M, Justiniani-Basaran H, Lugnier C, Orallo F (2006) Study the of the mechanisms involved in the vasorelaxation induced by (−)- epigallocatechin-3-gallate in rat aorta. Br J Pharmacol 147:269–280CrossRef Alvarez E, Campos-Toimil M, Justiniani-Basaran H, Lugnier C, Orallo F (2006) Study the of the mechanisms involved in the vasorelaxation induced by (−)- epigallocatechin-3-gallate in rat aorta. Br J Pharmacol 147:269–280CrossRef
34.
go back to reference Chen ZY, Law WI, Yao XQ, Lau CW, Ho WK, Huang Y (2000) Inhibitory effects of purified green tea epicatechins on contraction and proliferation of arterial smooth muscle cells. Acta Pharmacol Sin 21:835–840 Chen ZY, Law WI, Yao XQ, Lau CW, Ho WK, Huang Y (2000) Inhibitory effects of purified green tea epicatechins on contraction and proliferation of arterial smooth muscle cells. Acta Pharmacol Sin 21:835–840
35.
go back to reference Martin W, Furchgott RF, Villani GM, Jothianandan D (1986) Depression of contractile responses in rat aorta by spontaneously released endothelium-derived relaxing factor. J Pharmacol Exp Ther 237:529–538 Martin W, Furchgott RF, Villani GM, Jothianandan D (1986) Depression of contractile responses in rat aorta by spontaneously released endothelium-derived relaxing factor. J Pharmacol Exp Ther 237:529–538
36.
go back to reference Chen ZY, Su YL, Lau WI, Huang Y (1999) Endothelium-dependent contraction and direct relaxation induced by baicalein in rat mesenteric artery. Euro J Pharmacol 374:41–47CrossRef Chen ZY, Su YL, Lau WI, Huang Y (1999) Endothelium-dependent contraction and direct relaxation induced by baicalein in rat mesenteric artery. Euro J Pharmacol 374:41–47CrossRef
37.
go back to reference Wyse GD (1990) On the “normalization” of active developed force of isolated helical strips of muscular and elastic arteries for variation in wall thickness. J Pharmacol Methods 4:313–326CrossRef Wyse GD (1990) On the “normalization” of active developed force of isolated helical strips of muscular and elastic arteries for variation in wall thickness. J Pharmacol Methods 4:313–326CrossRef
38.
go back to reference Li Z, Wang Y, Vanhoutte PM (2011) Epigallocatechin Gallate elicits contractions of the isolated aorta of the aged spontaneously hypertensive rat. Basic Clin Pharmacol Toxicol 109(1):47–55CrossRef Li Z, Wang Y, Vanhoutte PM (2011) Epigallocatechin Gallate elicits contractions of the isolated aorta of the aged spontaneously hypertensive rat. Basic Clin Pharmacol Toxicol 109(1):47–55CrossRef
39.
go back to reference Gendron ME, Théorêt JF, Mamarbachi AM et al (2010) Late chronic catechin antioxidant treatment is deleterious to the endothelial function in aging mice with established atherosclerosis. Am J Physiol Heart Circ Physiol 298(6):H2062–H2070CrossRef Gendron ME, Théorêt JF, Mamarbachi AM et al (2010) Late chronic catechin antioxidant treatment is deleterious to the endothelial function in aging mice with established atherosclerosis. Am J Physiol Heart Circ Physiol 298(6):H2062–H2070CrossRef
Metadata
Title
Endothelium/nitric oxide mechanism mediates vasorelaxation and counteracts vasoconstriction induced by low concentration of flavanols
Authors
Annalisa Aggio
Davide Grassi
Eugenia Onori
Antonio D’Alessandro
Francesco Masedu
Marco Valenti
Claudio Ferri
Publication date
01-02-2013
Publisher
Springer-Verlag
Published in
European Journal of Nutrition / Issue 1/2013
Print ISSN: 1436-6207
Electronic ISSN: 1436-6215
DOI
https://doi.org/10.1007/s00394-012-0320-x

Other articles of this Issue 1/2013

European Journal of Nutrition 1/2013 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.